Contribution of arylsulfatase A mutations located on the same allele to enzyme activity reduction and metachromatic leukodystrophy severity

摘要: The occurrence of different mutations on the same arylsulfatase A allele is not uncommon, due to high frequency several variants, among which pseudodeficiency are particularly important. We identified a late infantile metachromatic leukodystrophy patient carrying one new E253K mutation and known T391S polymorphism, other common P426L mutation, usually associated with adult or juvenile form disease, N350S *96A>G mutations. To analyze contribution located enzyme activity reduction, as well possible phenotype implications, we performed transient expression experiments using cDNAs separately in combination. Our results indicate that mutants containing multiple cause greater reduction ARSA than do corresponding single mutants, total deficiency likely sum reductions attributed each mutation. Consequently, may contribute and, therefore, degree disease severity. This important for alleles disease-causing mutations: these could play role affecting clinical phenotype.